Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH
8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and is associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested th...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004397 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841542483468615680 |
|---|---|
| author | Tobias Obermann Teri Sakshaug Vishnu Vignesh Kanagaraj Andreas Abentung Mirta Mittelstedt Leal de Sousa Lars Hagen Antonio Sarno Magnar Bjørås Katja Scheffler |
| author_facet | Tobias Obermann Teri Sakshaug Vishnu Vignesh Kanagaraj Andreas Abentung Mirta Mittelstedt Leal de Sousa Lars Hagen Antonio Sarno Magnar Bjørås Katja Scheffler |
| author_sort | Tobias Obermann |
| collection | DOAJ |
| description | 8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and is associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested that OG and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA-sequencing to correlate genome-wide distribution of OG with gene transcription in OGG1 and/or MUTYH-deficient cells. Our data identified moderate enrichment of OG in the genome that is mainly dependent on the genomic context and not affected by DNA glycosylase-initiated repair. Interestingly, no association was found between genomic OG deposition and gene expression changes upon loss of OGG1 and MUTYH. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that OG functions as a cellular stress sensor to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways. |
| format | Article |
| id | doaj-art-aae87b07b5444177b8163c2a99b4572a |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-aae87b07b5444177b8163c2a99b4572a2025-01-14T04:12:09ZengElsevierRedox Biology2213-23172025-02-0179103461Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYHTobias Obermann0Teri Sakshaug1Vishnu Vignesh Kanagaraj2Andreas Abentung3Mirta Mittelstedt Leal de Sousa4Lars Hagen5Antonio Sarno6Magnar Bjørås7Katja Scheffler8Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, 7006, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Proteomics and Modomics Experimental Core (PROMEC), NTNU and the Central Norway Regional Health Authority, N-7491, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Proteomics and Modomics Experimental Core (PROMEC), NTNU and the Central Norway Regional Health Authority, N-7491, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Centre for Embryology and Healthy Development, University of Oslo, Oslo, 0373, Norway; Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, 0424, NorwayDepartment of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, 7006, Trondheim, Norway; Corresponding author. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491, Trondheim, Norway.8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and is associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested that OG and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA-sequencing to correlate genome-wide distribution of OG with gene transcription in OGG1 and/or MUTYH-deficient cells. Our data identified moderate enrichment of OG in the genome that is mainly dependent on the genomic context and not affected by DNA glycosylase-initiated repair. Interestingly, no association was found between genomic OG deposition and gene expression changes upon loss of OGG1 and MUTYH. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that OG functions as a cellular stress sensor to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways.http://www.sciencedirect.com/science/article/pii/S2213231724004397 |
| spellingShingle | Tobias Obermann Teri Sakshaug Vishnu Vignesh Kanagaraj Andreas Abentung Mirta Mittelstedt Leal de Sousa Lars Hagen Antonio Sarno Magnar Bjørås Katja Scheffler Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH Redox Biology |
| title | Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH |
| title_full | Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH |
| title_fullStr | Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH |
| title_full_unstemmed | Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH |
| title_short | Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH |
| title_sort | genomic 8 oxoguanine modulates gene transcription independent of its repair by dna glycosylases ogg1 and mutyh |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004397 |
| work_keys_str_mv | AT tobiasobermann genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT terisakshaug genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT vishnuvigneshkanagaraj genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT andreasabentung genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT mirtamittelstedtlealdesousa genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT larshagen genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT antoniosarno genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT magnarbjøras genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh AT katjascheffler genomic8oxoguaninemodulatesgenetranscriptionindependentofitsrepairbydnaglycosylasesogg1andmutyh |